Evidence for a crucial modulating role of the sodium channel in the QTc prolongation related to antipsychotics.

Blockade of the cardiac hERG channel is recognized as the main mechanism underlying the QT prolongation induced by many classes of drugs, including antipsychotics. However, antipsychotics interact with a variety of other pharmacological targets that could also modulate cardiac function. The present study aims to identify those key factors involved in the QT prolongation induced by antipsychotics.

It might be a big family but the pain remains-last chance saloon for selective 5-HT receptor ligands?

The following brief overview reflects our own opinion of where the most likely advances to treating pain (unrelated to IBS and migraine) may come from with respect to ligands directly interacting with specific 5-HT receptors. It is fully appreciated, and possibly more likely, that 5-HT plays a modulatory role in the mediation of analgesic effects of certain compounds, for example tricyclic antidepressants and the newer, safer class of serotonin/noradrenaline re-uptake inhibitors, for example duloxetine and milnacipran. However, we find that recent pre-clinical findings highlight the potential of peripherally acting 5-HT(1) and 5-HT(2A) receptor agonists and centrally penetrating 5-HT(7) receptor agonists to reduce chronic pain.

Study focuses in on potential cause of antipsychotic-induced diabetes.

First-generation antipsychotic drugs, efficacious in reducing the "positive" syndrome of schizophrenia, carried serious motor side effects, such as immobility and Parkinsonism. While second-generation antipsychotics have reduced the incidence of such effects, they are not without risk. It has come to light that both first- and second-generation antipsychotics are associated with weight gain and type 2 diabetes.

Amphetamine promotes task-dependent recovery following focal cortical ischaemic lesions in the rat.

This study investigated the effect of amphetamine (AMP) on skilled forelimb use following focal cortical ischaemic lesions in the rat. Unilateral lesions were produced by a novel method of intracortical microinjection of endothelin-1 (ET-1), intended to principally target the forelimb representation zone in primary motor-primary somatosensory cortex. Lesions were placed in the hemisphere contralateral to the preferred limb and produced deficits in skilled forelimb use on two tasks: the paw reach (PR) test and the foot fault (FF) test.

Locomotor activity detects subunit-selective effects of agonists and decahydroisoquinoline antagonists at AMPA/kainic acid ionotropic glutamate receptors in adult rats.

Rationale: In vitro studies have identified a series of decahydroisoquinoline compounds with differential selectivity for the subunits that comprise AMPA/kainic acid receptors. Compounds have been identified that have preferential activity at AMPA receptors (LY302679), whereas others (LY377770) have affinity for GluR5-kainic acid preferring subunit, which is activated by ATPA and kainic acid.

Objectives: These studies set out to determine if locomotor activity could differentiate these profiles in vivo.

The effects of intracortical endothelin-1 injections on skilled forelimb use: implications for modelling recovery of function after stroke.

Different methods of inducing experimental brain lesions can result in distinct neuropathological sequelae. This could be of consequence in attempts to establish animal models of recovery of function following stroke, as differences in the progression of experimental lesion pathology may have an impact on the magnitude and rate of recovery of function observable with any particular lesioning method. In the present study, a novel method of producing a focal ischaemic lesion by intracortical microinjection of endothelin-1 (ET-1) was compared with excitotoxic (microinjection of quinolinic acid) and mechanical (aspiration) lesioning procedures.

Bicyclo[2.2.1]heptanes as novel triple re-uptake inhibitors for the treatment of depression.

A series of substituted naphthyl containing chiral [2.2.1] bicycloheptanes were prepared utilizing asymmetric Diels-Alder chemistry.

Group II metabotropic glutamate receptor antagonists LY341495 and LY366457 increase locomotor activity in mice.

The group II metabotropic glutamate receptor (mGluR) antagonists LY341495 and LY366457 were profiled for their effects on locomotor activity in mice. Both compounds significantly increased locomotor activity. Observational studies showed that rearing was also selectively increased.

Behavioural pharmacology of polygalasaponins indicates potential antipsychotic efficacy.

Polygalasaponins were extracted from a plant (Polygala tenuifolia Willdenow) that has been prescribed for hundreds of years to treat psychotic illnesses in Korean traditional medicine. Previous in vitro binding studies suggested a potential mechanism for its antipsychotic action, as polygalasaponin was shown to have an affinity for both dopamine and serotonin receptors [Psychopharmacol. Bull.